As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. ...We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.
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•Antibody neutralization is inversely associated with SARS-CoV-2 in nasopharyngeal swabs•Antigen-specific B cells positively associate with anti-SARS-CoV-2 humoral immunity•SARS-CoV-2 neutralizing antibodies are present in patients with higher specific T cells•Antigen-specific B and T cells are features of SARS-CoV-2 immunity in children
Cotugno et al. show that neutralizing antibodies affect SARS-CoV-2 viral load in infected children. Antigen-specific B and T cells are positively associated with virus neutralization. This information provides a basis for defining SARS-CoV-2 adaptive responses in children.
Microvesicles (MVs) are large extracellular vesicles differing in size, cargo and composition that share a common mechanism of release from the cells through the direct outward budding of the plasma ...membrane. They are involved in a variety of physiological and pathological conditions and represent promising biomarkers for diseases. MV heterogeneity together with the lack of specific markers had strongly hampered the development of effective methods for MV isolation and differential centrifugation remains the most used method to purify MVs. In this study, we analysed the capacity of the differential centrifugation method to isolate MVs from cell-conditioned medium using flow cytometry and TEM/AFM microscopy. We found that the loss of MVs (general population and/or specific subpopulations) represents a major and underestimate drawback of the differential centrifugation protocol. We demonstrate that the choice of the appropriate rotor type (fixed-angle vs swinging-bucket) and the implementation of an additional washing procedure to the first low-speed centrifugation step of the protocol allow to overcome this problem increasing the total amount of isolated vesicles and avoiding the selective loss of MV subpopulations. These parameters/procedures should be routinely employed into optimized differential centrifugation protocols to ensure isolation of the high-quantity/quality MVs for the downstream analysis/applications.
Background
Due to the failure of the “old Mason loop,” the mini-gastric bypass (MGB) has been viewed with skepticism. During the past 12 years, a growing number of authors from around the world have ...continued to report excellent short- and long-term results with MGB.
Methods
One university center, three regional hospitals, and two private hospitals participated in this study. From July 2006 to December 2012, 475 men (48.8 %) and 499 women (51.2 %) underwent 974 laparoscopic MGBs. The mean age of these patients was 39.4, and their preoperative body mass index was 48 ± 4.58 kg/m
2
. Type 2 diabetes mellitus (T2DM) affected 224 (22.9 %) of the 974 patients, whereas 291 of the 974 patients (29.8 %) presented with hypertension. The preoperative gastrointestinal status was explored in all the patients through esophagogastroduodenoscopia. The major end points of the study were definitions of both MGB safety and efficacy in the long term as well as the endoscopic changes in symptomatic patients eventually produced by surgery.
Results
The rate of conversion to open surgery was 1.2 % (12/974), and the mortality rate was 0.2 % (2/974). The perioperative morbidity rate was 5.5 % (54/974), with 20 (2 %) of the 974 patients requiring an early surgical revision. The mean hospital length of stay was 4.0 ± 1.7 days. At this writing, 818 patients are being followed up. Late complications have affected 74 (9 %) of the 818 patients. The majority of these complications (66/74, 89.1 %) have occurred within 1 year after surgery. Bile reflux gastritis was symptomatic, with endoscopic findings reported for 8 (0.9 %) and acid peptic ulcers for 14 (1.7 %) of the 818 patients. A late revision surgery was required for 7 (0.8 %) of the 818 patients. No patient required revision surgery due to biliary gastritis. At 60 months, the percentage of excess weight loss was 77 ± 5.1 %, the T2DM remission was 84.4 %, and the resolution of hypertension was 87.5 %.
Conclusions
Despite initial skepticism, this study, together with many other large-scale, long-term similar studies from around the world (e.g., Taiwan, United States, France, Spain, India, Lebanon) demonstrated the MGB to be a short, simple, low-risk, effective, and durable bariatric procedure.
We report 10 cases of status epilepticus (SE) in patients with posterior reversible encephalopathy syndrome (PRES). In all cases, SE brought PRES to medical attention. The majority of the cases had ...focal-onset complex partial SE. Complete resolution of SE was achieved after combined treatment of PRES and SE in all cases. SE in the setting of PRES carries a favorable prognosis but requires timely recognition and treatment of the course of PRES.
Summary
Low‐affinity immunoglobulin (Ig)G with potential autoreactivity to lymphocytes and hypergammaglobulinaemia have been described previously in HIV‐1‐infected patients. Whether such antibodies ...increase after challenging the immune system, for example with an immunization, is not known. In the present study, the modulation of antibodies with low affinity and potential autoreactivity was evaluated after 2012–13 seasonal flu vaccination with a simple empirical laboratory test measuring the titres of anti‐lymphocyte antibodies (ALA) in two different models of secondary immunodeficiency: HIV‐1 vertically infected patients (HIV) and patients treated with immunosuppressive therapies after kidney transplantation (KT) compared to healthy individuals (HC). In parallel, the activation status of B cells and their degree of immune senescence was evaluated by measuring the B cell interleukin (IL)‐21R expression/plasma IL‐21 levels and the frequencies of mature‐activated (MA) and double‐negative (DN) B cells. A significant increase of ALA titres was observed after vaccination in HIV and KT but not in HC, and this correlated directly with the frequencies of both MA and DN and inversely with the B cell IL‐21R expression. This suggests that the quality of an immune response triggered by flu vaccination in HIV and KT may depend upon the activation status of B cells and on their degree of immune senescence. Further investigations are needed to verify whether high frequencies of MA and DN may also relate to increase autoimmunity after immunization in high‐risk populations.
Abstract Background The neurological manifestations of Systemic Lupus Erythematosus (SLE) are varied and incompletely described. A few case series report a benign idiopathic intracranial hypertension ...(IIH) related to SLE, which is responsive to immunotherapy. There are limited reports of patients with malignant cerebral edema, and diffuse white matter changes in the absence of central nervous system (CNS) vasculitis. Methods Case series from our tertiary care center and review of the relevant literature. Results Case one was a 32 year-old woman admitted with nausea, vomiting and cranial nerve palsies. Serology was significant for a diagnosis of probable SLE. MRI was performed and showed bilateral symmetric diffuse T2/FLAIR hyperintensities throughout the white matter and cerebral angiography was unremarkable. The patient developed recalcitrant cerebral edema with intracranial hypertension despite immunosuppressive therapies and subsequently expired. Post mortem evaluation showed a white matter inflammatory process, but no vascular changes consistent with CNS vasculitis. Case two was a 29 year-old woman with known SLE that presented with a loss of consciousness. Imaging included a CT that showed diffuse cerebral edema with white matter involvement and a normal cerebral angiogram. Again, despite maximal medical management the patient herniated resulting in death by neurologic criteria. Conclusions These two cases represent a syndrome of white matter changes and diffuse cerebral edema associated with SLE that have yet to be reported in the literature. It is unclear if this process has a similar pathology to SLE related IIH. Because this syndrome causes a fulminant cerebral edema, further research is needed to better understand the underlying pathology and identify potential treatment options.
Summary
Generation of antigen‐specific humoral responses following vaccination or infection requires the maturation and function of highly specialized immune cells in secondary lymphoid organs (SLO), ...such as lymph nodes or tonsils. Factors that orchestrate the dynamics of these cells are still poorly understood. Currently, experimental approaches that enable a detailed description of the function of the immune system in SLO have been mainly developed and optimized in animal models. Conversely, methodological approaches in humans are mainly based on the use of blood‐associated material because of the challenging access to tissues. Indeed, only few studies in humans were able to provide a discrete description of the complex network of cytokines, chemokines and lymphocytes acting in tissues after antigenic challenge. Furthermore, even fewer data are currently available on the interaction occurring within the complex micro‐architecture of the SLO. This information is crucial in order to design particular vaccination strategies, especially for patients affected by chronic and immune compromising medical conditions who are under‐vaccinated or who respond poorly to immunizations. Analysis of immune cells in different human tissues by high‐throughput technologies, able to obtain data ranging from gene signature to protein expression and cell phenotypes, is needed to dissect the peculiarity of each immune cell in a definite human tissue. The main aim of this review is to provide an in‐depth description of the current available methodologies, proven evidence and future perspectives in the analysis of immune mechanisms following immunization or infections in SLO.
In this review we aim to dissect novel technologies to analyze the immune system plasticity at tissue level. Such tools are needed in order to ‘study immune compartments as one inter‐dependent functional unit'. Our purpose is to highlight the advantages and the limitations of the most widely used approaches focusing on the importance of tissues analysis and the need of a computational approach.
In this work we report a study on the influence of innovative pulsed stresses utilizing an UV laser and a homemade generator of magnetic field on radish seeds (Raphanus sativus L.) growth. We ...analysed the seed germination and seedling growth. The UV pulsed laser was an excimer KrF operating at 248 nm, 23 ns of pulse duration, with a laser fluence of about 40 mJ/cm2. The generator of pulsed magnetic field was realized by the electric discharge on a coil of a high voltage capacitor of 150 μF, 60 kV . The magnetic field pulse waveform exhibited damped oscillations at 215 kHz with a maximum intensity of 400 mT . Groups of uniform radish seeds were exposed to laser pulses at five different doses: 30000 shots (KrF/1), 80000 shots (KrF/2), 145000 shots (KrF/3), 225000 shots (KrF/4) and 275000 shots (KrF/5). Other groups were exposed to magnetic field at eight different doses: 3600 shots (MF/1), 7200 shots (MF/2), 10800 shots (MF/3), 14400 shots (MF/4), 18000 shots (MF/5), 21600 shots (MF/6), 32400 kshots (MF/7) and 36000 shots (MF/8). Simultaneously, untreated seeds were used as control. All treatments were performed at room temperature. Both untreated and treated seeds were transferred in Petri dishes and followed for their germination and seedling growth up to 96 h. The results showed that the stress induced by UV laser photons brought a significant stimulation on root growth which may contribute to improve the performance and the productivity of the plants. On the contrary, all physical stresses induced by magnetic fields did not have effect on seed germination, as well as on cell elongation growth and on hypocotyls in comparison to control seeds.
Minimal standard heterotic string models Faraggi, A.E.; Manno, E.; Timirgaziu, C.
The European physical journal. C, Particles and fields,
04/2007, Letnik:
50, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Three generation heterotic string vacua in the free fermionic formulation gave rise to models with solely the MSSM states in the observable standard model charged sector. The relation of these models ...to Z2×Z2 orbifold compactifications dictates that they produce three pairs of untwisted Higgs multiplets. The reduction to one pair relies on the analysis of supersymmetric flat directions, which give a superheavy mass to the dispensable Higgs states. We explore the removal of the extra Higgs representations by using the free fermion boundary conditions, and hence we work directly at the string level, rather than in the effective low energy field theory. We present a general mechanism that achieves this reduction by using asymmetric boundary conditions between the left- and right-moving internal fermions. We incorporate this mechanism in explicit string models containing three twisted generations and a single untwisted Higgs doublet pair. We further demonstrate that an additional effect of the asymmetric boundary conditions is to substantially reduce the supersymmetric moduli space.
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